If parents have a son’s genes sequenced in hopes of explaining extreme muscle weakness, should they also be told whether he is likely to get Alzheimer’s disease as an adult? Should the child be told? When? How do answers to these questions shift for currently healthy adults? And should people be given more or less information depending on what they want to know?
As more and more people get large-scale sequencing as part of clinical care and research, the genetics community is struggling to define what to tell people about their own genomes. At the meeting of the American Society of Human Genetics, Holly Tabor at Seattle Children’s Hospital described an emerging approach to help people decide what results from their sequencing data they want to see and when.
Tabor has developed a web-based platform to manage the process. A website, called my46, explains types of mutations and lets users select whether they want to get results about variants associated with drug response, disease risk, and ancestry. They can also select to find out whether they carry mutations for heritable diseases. Users who originally decline to see certain results can change their minds later and also request appointments to talk with a genetic counselor at any time.
However, many ethicists are concerned that patients may not be able to gauge the harm learning sensitive information might cause. After all, patients may not realize how uncertain scientific knowledge is or overestimate potential treatments. Such is the reasoning behind ethicists who recommend “justified paternalism”, with results shared not based solely on patients’ stated preference but according to clinicians’ professional judgment.
There is little concrete information about how patients respond to their genetic information. One study published early last year found little evidence for increased anxiety in subjects who received direct-to-consumer genome profiling, but sequencing studies have provide more extensive information.
At the end of last year, the National Human Genome Research Institute funded seven projects, including Tabor’s, to figure out how people react to information in their genomes. For Tabor’s project, about 200 people who are already participating in exome-sequencing projects are being recruited to test the impact of the my46 platform. The study will track web users and a control group according to their psychological adjustment to sequencing data, reports of depression and healthcare utilization.
No matter how results are returned to patients, the genetics community will need a way to classify variants. Jim Evans, a medical geneticist at the University of North Carolina, described “bins” for mutations: those of unknown significance, those for which a patient can take action, those representing credible disease risk, those of reproductive significance. Earlier this year, the American College of Medical Genetics began drafting recommendations about what information must be shared with patients. If a mutation is very likely to lead to disease and especially if treatments are available, geneticists are generally obligated to tell patients. But for many variants, potential outcomes are uncertain or treatments unavailable.
Even those broad categories are hard to sort, and different medical centers follow different procedures. Amy McGuire of Baylor College of Medicine told meeting attendees that the current lack of consensus could be a strength rather than a weakness. It gives researchers more ways to find better solutions.